Is CACNG8 p.Tyr152Ser (c.455A>C) pathogenic?

CACNG8 p.Tyr152Ser (c.455A>C) is classified Uncertain significance in CACNG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: ambiguous (0.4363); Absent from gnomAD v4.1.

How common is CACNG8 p.Tyr152Ser (c.455A>C) in the general population?

CACNG8 p.Tyr152Ser (c.455A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CACNG8 p.Tyr152Ser (c.455A>C)?

AlphaMissense predicts ambiguous (score 0.4363) — an in-silico prediction, not a clinical call.

CACNG8 p.Tyr152Ser

c.455A>C · VCV4647646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4363	ambiguous
REVEL	0.606	indeterminate
SaProt	LLR -8.64	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,237 bp · p 7.3e-10 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CACNG8
Protein: p.Tyr152Ser
Coding: c.455A>C
MANE Select: NM_031895
Type: single nucleotide variant
Location: chr19:53979954 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.04

Full CACNG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNG8 p.Ala183Ser Uncertain significance ★ ⚠ same type
CACNG8 p.Ala289Ser Uncertain significance ★ ⚠ same type
CACNG8 p.Ala323Val Uncertain significance ★ ⚠ same type
CACNG8 p.Ala325Thr Uncertain significance ★ ⚠ same type
CACNG8 p.Ala362Ser Uncertain significance ★ ⚠ same type
CACNG8 p.Ala389Thr Uncertain significance ★ ⚠ same type
CACNG8 p.Ala392Thr Uncertain significance ★ ⚠ same type
CACNG8 p.Ala400Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cacng8-p-tyr152ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown